Oncotarget

Research Papers:

SMAD7 loci contribute to risk of hepatocellular carcinoma and clinicopathologic development among Chinese Han population

Jiansong Ji _, Min Xu, Zhongwei Zhao, Jianfei Tu, Jun Gao, Chenying Lu, Jingjing Song, Weiqian Chen, Minjiang Chen, Xiaoxi Fan, Xingyao Cheng, Xilin Lan and Jie Li

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Oncotarget. 2016; 7:22186-22192. https://doi.org/10.18632/oncotarget.8065

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Abstract

Jiansong Ji1,*, Min Xu1,*, Zhongwei Zhao1,*, Jianfei Tu1,*, Jun Gao2,*, Chenying Lu1, Jingjing Song1, Weiqian Chen1, Minjiang Chen1, Xiaoxi Fan1, Xingyao Cheng1, Xilin Lan1, Jie Li3

1Department of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, Zhejiang, P.R. China

2Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital Affiliated with Capital Medical University, Beijing, P.R. China

3The First Affiliated Hospital, Chongqing Medical University, Chongqing, P.R. China

*These authors contributed equally to this work

Correspondence to:

Jiansong Ji, e-mail: [email protected]

Keywords: HCC, mothers against decapentaplegic homolog 7 (SMAD7), transforming growth factor beta (TGF-β), risk, SNP

Received: November 05, 2015     Accepted: February 05, 2016     Published: March 14, 2016

ABSTRACT

Genome-wide association studies (GWAS) have identified three loci at 18q21 (rs4939827, rs7240004, and rs7229639), which maps to SMAD7 loci, were associated with risk of diseases of the digestive system. However, their associations with hepatocellular carcinoma (HCC) risk remain unknown. A case-control study was conducted to assess genetic associations with HCC risk and clinicopathologic development among Chinese Han population. Three SNPs were genotyped among 1,000 HCC cases and 1,000 controls using Sequenom Mass-ARRAY technology. We observed statistically significant associations for the three SMAD7 loci and HCC risk. Each copy of minor allele was associated with a 1.24–1.36 fold increased risk of HCC. We also found that significant differences were observed between rs4939827 and clinical TNM stage and vascular invasion, as well as rs7240004 and vascular invasion. We also established a genetic risk score (GRS) by summing the risk alleles. The GRS was significantly associated with increased risk of HCC and vascular invasion. Our data revealed the SMAD7 loci is associated with HCC susceptibility and its clinicopathologic development.


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